Asthma Chronic Inflammatory Disorder Cells Elements Airways Involved Biology Essay

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Asthma is a chronic inflammatory disorder wherein most cells and elements of the airways are involved. The chronic inflammation involves increased airway hyperresponsiveness and leads to frequent episodes of wheezing, breathlessness, chest tightness, and coughing, most notably at night or in the early morning. These episodes are usually observed be at a very large scale, however has a high non-uniformity of airflow obstruction. Hence, these episodes can be reversed either spontaneously or with treatment. In chronic airway inflammation of asthma there is high infiltration by T-lymphocytes of the T-helper (Th) type 2 phenotype, eosinophils, macrophages/monocytes and mast cells in the airway walls. Also, during exacerbations, there is acute inflammation with a sudden increase in eosinophils and neutrophils infiltration.

Inflammatory processes associated with asthma include airway infiltration with inflammatory cells of the immune system, airway epithelial wall disruption, subepithelial deposition of matrix proteins like collagen, fibronectin, tenascin and other elements, hypertrophy and hyperplasia of airway smooth muscle increase in vasculature of airway, and increase in goblet cells and other mucus secreting cells and eventual hyper-secretion of mucus in the airways. The inflammatory cells include T-lymphocytes, mast cells, and eosinophils. These inflammatory processes are caused mainly by T-helper type 2 (TH2) lymphocytes. The TH2 cells secrete cytokines and chemokines that in turn lead to activation and recruitment of eosinophils (interleukin [IL]-3, IL-5, granulocyte/macrophage colony-stimulating factor) and mast cells (IL-9, IL-4), and permit inflammatory cell influx into the airways. Asthma is partly a consequence of imbalance in TH2 lymphocytes rather than T-helper type 1 (TH1) lymphocytes which is responsible for delayed hypersensitivity reactions.

In recent past, the treatment of asthma has mainly included alleviating the symptoms rather than curing the disease. Pulmonary route of delivery of drugs has been the mainstay of treatment mode in the past for temporary relief of exacerbations in asthma. The most popular drugs used include β2 adrenergic receptor agonists, such as salbutamol sulphate, formoterol fumarate and salmeterol xinafoate. These are recently been administered along with a 2nd class of drugs called corticosteroids, and also other drugs. The table 1 presents a list of the most widely used β2 adrenoceptor agonist drugs in asthma treatment.

Onset of Action

Duration of action







Salbutamol (Albuterol)





Table 1: Onset and duration of action of inhaled β2 agonists.

Drugs used in the treatment of asthma

Anti-inflammatory drugs are by far the most important class of drugs for asthma treatment. These are mainly glucocorticoids and theophylline. However, most formulations in dry powder inhalers (DPIs) and pressurized metered dose inhalers (pMDIs) make use of short or long-acting β2-adrenoceptor agonists. Table-2 summarizes studies on the efficacy of the drugs in control of asthma, particularly with reduction in inflammatory cells of immune system.

Asthma Drugs

Control of Asthma


Inhaled corticosteroids



Sodium cromoglycate



Sodium nedocromil



Short acting β2 agonists



Long acting β2 agonists









Leukotriene Synthesis Inhibitors



CysLTs receptors antagonists



Furosemide + salycilic acid






Table 2: Bronchial anti-inflammatory activity of asthma drugs. + effective, - not effective, +/- controversial effect, ? no data available, Biopsy= reduction in bronchial inflammatory cell number with chronic treatment.

Each class of drug has a different mode of action and contributes to lessening the symptoms of asthma via different mechanisms. Consequently, depending upon the physicochemical properties of the drugs, they need to be formulated in different ways. The most widely used routes of administration of anti-asthmatic drugs are oral route via the gastro intestinal tract and the pulmonary route, which is a more direct route of transporting the drugs to their site of action. The next section summarizes the different classes of drugs, the drugs in market that fall in these classes, the different formulations available in the market and the mechanisms by which these classes of drugs act to perform their anti-inflammatory and bronchodilatory actions on smooth muscles in the respiratory tract.

Review of the Important Classes of Drugs used in Dry powder Inhalers and Other Formulations for Asthma Treatment :

Class 1. Short Acting β2-adrenoceptor agonist (Salbutamol, Terbutaline):

Salbutamol (Albuterol) Sulphate, a moderately selective β2-adrenoceptor agonist, is a racemic mixture of R- and S-isomers. Salbutamol Sulphate is widely used as a bronchodilator and is indicated for the management of asthma exacerbations or other chronic obstructive airway diseases. Salbutamol Sulphate is similar in structure to terbutaline, but exhibits less cardiac stimulation and more prolonged bronchodilation than isoproterenol or metaproterenol. It is a short-acting β2 agonist and considered as first line therapy for mild intermittent asthma during pregnancy (according to the 2004 guidelines of the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group).

Salbutamol (Albuterol) Sulphate's innovator is Boehringer Ingelheim-Global and appears world-wide under the brand names Combivent and Duoneb.

Salbutamol Sulphate stimulates receptors of the smooth muscle in the lungs, uterus, and vasculature supplying skeletal muscle. Salbutamol Sulphate is racemic beta-agonist, comprised of an equal mixture of R- and S-isomers. The R-isomer, known as levalbuterol Sulphate, is primarily responsible for bronchodilation.

Intracellularly, the actions of Salbutamol Sulphate are mediated by cyclic AMP, the production of which is augmented by β2-stimulation. Salbutamol Sulphate is believed to work by activating adenylate cyclase, the enzyme responsible for generating cyclic AMP, an intracellular mediator. Increased cyclic AMP leads to activation of protein kinase A, which inhibits phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in relaxation. The net result of β2-receptor agonism in the lungs is relaxation of bronchial and tracheal smooth muscles, which in turn relieves bronchospasm, reduces airway resistance, facilitates mucous drainage, and increases vital capacity.

Salbutamol Sulphate can also inhibit the degranulation and subsequent release of inflammatory autocoids from mast cells. Stimulation of β2-receptors on peripheral vascular smooth muscle can cause vasodilation and a modest decrease in diastolic blood pressure. Salbutamol Sulphate is an effective adjunctive treatment for hyperkalemia; β2-adrenergic stimulation results in intracellular accumulation of serum potassium due to stimulation of the Na/K ATPase pump, leading to moderate degrees of hypokalemia.

Class 2. Long Acting β2-adrenoceptor agonist (Formoterol, Salmeterol) :

Long acting β2-adrenoceptor agonists (LABAs) relax bronchial smooth muscle and thereby elicit bronchodilation in patients with asthma. Recommended for use in combination with inhaled corticosteroids, they provide additional benefits to those patients inadequately controlled with corticosteroids alone and may ultimately permit tapering of the dose of inhaled steroid. The drugs included in this class are Formoterol and salmeterol. Formoterol has a rapid onset of action (1-3 minutes), which is comparable with that of short-acting β2-agonists (e.g. salbutamol and terbutaline), and a mean duration of action of 12 hours following inhalation of a single dose. Thus patients can experience prolonged bronchodilation with formoterol. Risk associated with use of formoterol includeprolongation of QTc interval, paradoxical bronchospasm and hypokalaemia. Salmeterol, on the other hand has a slow onset of action, but its effect on bronchodilation lasts upto 12 hours. This permits twice-daily dosing and enables good control of nocturnal asthma.

Class 3. Inhaled Corticosteroids (Beclometasone, Budenoside, Ciclesonide, Fluticasone, Mometasone) :

This is the most potent class of drugs for the treatment of asthma. In most asthmatic patients adequate doses of inhaled glucocorticoids, particularly if combined with long-acting bronchodilators, allow systemic glucocorticoids to be reduced or withdrawn completely. Glucocorticoids consistently lessen airway hyperesponsiveness in asthma. Indeed, long-term treatment with glucocorticoids reduced airway responsiveness to histamine, cholinergic agonists, allergens (affecting both early and late responses), exercise, fog, cold air, bradykinin, adenosine, and irritants such as sulfur dioxide and metabisulfites. Treatment benefits include not only reduced sensitivity of airways to spasmogens, but also limiting of maximal narrowing of the airway in response to a spasmogen. The reduction in airway hyperesponsiveness may not be maximal until treatment has been given for several months. The magnitude of the reduction varies, and airway responsiveness can remain abnormal. When therapy is discontinued airway responsiveness usually returns to pretreatment levels.

Fig: The mechanism of glucocorticoid action.

Fig: Cross-talk between glucocorticoids and long acting b2-agonists.

Class 4. Leukotriene Inhibitors (Montelukast, Zafirlukast, Zileuton) :

Leukotriene inhibitors are the first new class of medications for the treatment of persistent asthma that have been approved by the U.S. Food and Drug Administration in more than two decades. Leukotrienes are synthesized in response to many triggers, including receptor activation, antigen-antibody interaction, physical stimuli such as cold, and any stimulation that increases intercellular calcium. These potent inflammatory mediators promote neutrophil-endothelial interactions, inducing bronchoconstriction and enhancing airway hyperresponsiveness. They also stimulate smooth muscle hypertrophy, mucus hypersecretion, and the influx of eosinophils into airway tissues. Therefore, inhibition of leukotrienes potentially plays an important role in the treatment of asthma and other allergic conditions such as allergic rhinitis, atopic dermatitis, and chronic urticaria.

Leukotriene inhibitors are either leukotriene receptor antagonists or leukotriene synthesis inhibitors. Leukotriene receptor antagonists selectively block cysteinyl leukotriene (cysLT1) receptor, whereas leukotriene synthesis inhibitors block 5-lipoxygenase activity. These inhibit both bronchoconstrictive and inflammatory effects of the leukotrienes, which are inflammatory mediators associated with asthma pathophysiology. Montelukast has a rapid onset of action, minimal side effect profile and is administered orally. Thus it is easily formulated and bears no complications of inhaler devices.

Class 5. Anticholinergics :

Class 6. Theophylline :

Effect of Combination of classes (Corticosteroids and β2-adrenoceptor agonists) used in pMDI and DPI formulations in Asthma treatment :

In recent times there have been several formulations that include a combination of drugs of different classes, owing to their complementary modes of action.Fluticasone, for example, increases the responsiveness and number of β2-adrenoceptors, and therefor has the potential to elevate the efficacy of salmeterol. It is proposed in various studies that salmeterol enhances the ability of fluticasone to induce apoptosis in eosinophils by 3-5 folds. It is also reported that long acting β2-adrenoceptor agonists may prime the corticosteroid receptor for ligand binding and, enhance the translocation of the corticosteroid-receptor complex to the nucleus. However, the data available in support of this is not sufficient and additional studies are required to demonstrate that salmeterol exerts any meaningful anti-inflammatory activity in-vivo.

Figure 2. In vitro evidence suggests that ß2-agonists may prime inactive corticosteroid receptors (2A) and that corticosteroids may increase the number of ß2-receptors and their sensitivity to ß2-agonists (2B). Primed receptors are activated more easily by corticosteroids, and less steroid is required to convert the primed receptor to an active receptor. This priming effect could explain why a lower dosage of an inhaled corticosteroid plus a long-acting ß2-agonist is more effective than a higher dosage of an inhaled corticosteroid alone.

Salbutamol Sulphate

Salbutamol Sulphate is a short-acting β2 adrenoceptor agonist. The form of the drug used in formulating medicines is a racemic mixture of R- and S-isomers. The R-isomer, known as levalbuterol Sulphate, is primarily responsible for bronchodilation. Salbutamol Sulphate has been widely used owing to its ability to act as a bronchodilator and give immediate relief in cases of asthma exacerbations or other chronic obstructive airway diseases. Salbutamol Sulphate has a similar structure to terbutaline, but is more effective in the ability to bronchodilate for longer period of time than terbutaline. It is also the main drug for treatment in mild asthma in conditions of pregnancy in females (according to the 2004 guidelines of the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group).

Salbutamol Sulphate's innovator is Boehringer Ingelheim-Global and their products with Salbutamol sulphate appear in the world market under the brand names Combivent and Duoneb.

Intracellularly, the actions of Salbutamol Sulphate are mediated by cyclic AMP, the production of which is augmented by β2-stimulation. Salbutamol Sulphate works to relax the smooth muscles and bronchodilate the airway walls via the following mechanism: It activates adenylate cyclase which is the enzyme responsible for generating cyclic AMP, an intracellular mediator. Elevated levels of cyclic AMP causes an activation of protein kinase A (PKA). PKA inhibits phosphorylation of smooth muscle protein, myosin and the intracellular calcium ion concentration drops. This is the event that leads to smooth muscle relaxation in the bronchi and trachea, alleviates bronchospasm, permits freeflow of air through the airways, decreases mucous concentration by effective drainage and subsequently improves vital capacity.

Another mechanism by which Salbutamol Sulphate lowers bronchial hyper reactivity (BHR) and airway inflammation is by inhibition of degranulation and subsequent release of inflammatory autocoids from mast cells.

Delivery devices (Martin J Telko RESPIRATORY CARE •€ SEPTEMBER 2005 VOL 50 NO 9)

Inhalation drug delivery systems can be divided into 3 principal categories: pressurized metered-dose inhalers (pMDIs), DPIs, and nebulizers.

Nebulizers : Nebulizers are distinctly different from both pMDIs and DPIs. Nebulizers incorporate dissolved or suspended drug in a polar solvent, mainly water. The aerosol is continuously delivered over extended period of time and is useful in case of severe asthma for continuous exposure of airways to drug. Nebulizers are used mostly in emergency cases and in hospitals, and due to their bulky size and inconvenience to carry around, they are not generally used for chronic-disease management.

pMDI : pMDI is by far the most widely used device owing to its convenience in handling and ease of administration of dose. Because a pMDI is pressurized, it emits the dose at high velocity, leading to deposition in the oropharyngeal region and the lower airways devoid of the dose. Thus, pMDIs require careful coordination of actuation and inhalation. There are several enhancements to the pMDI design such as the use of spacers for children. Problems reported with use of pMDI include improper administration leading to wrong dose, and the propellant like CFC and cosolvents, may extract organic compounds from the device components.

DPIs : DPIs are drug delivery devices for pulmonary drug delivery that contain solid drug particles in the DPI device that is fluidized when the patient inhales. The development of DPIs has come about after there were several disadvantages with the use of pMDIs reported, such as emission of ozone-depleting and greenhouse gases (chlorofluorocarbons and hydrofluoroalkanes, respectively) that are used as propellants, and inability to deliver macromolecules and products of biotechnology. DPIs are easier to use, more stable and efficient systems. DPIs are activated by the patient's inspiratory airflow, hence they do not require propellent nor do they need to have coordination between actuation and inhalation. The resultant in better lung delivery than with pMDIs. Since DPIs are typically formulated as one-phase, solid particle blends, they are also preferred from a stability and processing standpoint. Also, due to lower energy state of the powder formulation, there is reduction in the rate of chemical degradation and reaction with contact surfaces.

Table 1. Summary of the features of Dry Powder Inhalers in comparison with Metered-Dose Inhalers:

Advantages of the Dry Powder Inhaler

Disadvantages of the Dry Powder Inhaler

Environmental sustainability, propellant-free design

Deposition efficiency dependent on patient's inspiratory airflow

Little or no patient coordination required

Potential for dose uniformity problems

Formulation stability

Development and manufacture more complex/expensive

Principle of operation :

Fig. 1. Principle of dry powder inhaler design.

The formulation typically consists of micronized drug blended with larger carrier particles, dispensed by a metering system. An active or passive dispersion system entrains the particles into the patient's airways, where drug particles separate from the carrier particles and are carried into the lung.

Most DPIs employ drug powder in the inhalation range, i.e. between 0.5-5µm diameter. This drug is blended with larger carrier particles such as lactose of typically 60µm size. Carrier particles like lactose help prevent agglomeration of the API powder and improves the flowability of the DPI formulation. The dry powder aerosols are generated when the powder in static powder bed is moved and dispersed in the stream of air. Movement can be brought about by several mechanisms. The most notable of these is based on the patient's inspiratory flow. The patient activated the DPI and from the mouth of the device, the patient inhales. This causes airflow in the device with turbulence and shear. The air fluidizes the powder in the static bed and the powder is dispersed. It enters the patient's respiratory tract along with the inhaled. The carrier particles being large and bulky, get trapped in the oropharynx and are cleared, whereas the drug particles attached to the carriers, owing to their small size and the force of airflow, get detached from the carriers and enter the lower airways. Thus deposition in the lungs is determined by the patients' inspiratory flow rate and is variable from patient to patient, although the device and formulation are the same. One of the major problems with the use of DPI, observed commonly with currently available DPI formulations is the inappropriate adhesion forces between drug and carrier particles. With adhesive forces lower than optimum, the drug gets detached very soon and does not enter the patient's respiratory airways; whereas with adhesive forces higher than optimum, the drug is not released optimally, and gets deposited in oropharynx along with the carrier. 24-26 Inadequate drug/carrier separation is one of the main explanations for the low deposition efficiency encountered with DPIs.27

Also, dose uniformity is a challenge in the performance of DPIs as this varies with patients' inspiratory airflow. To overcome the problem of dose uniformity, various studies on dispersion mechanisms are currently being done globally. Some of these include several power-assisted devices like pneumatic, impact force, and vibratory.


Powder properties can vary widely. Powder features, such as the physicochemical properties and morphology of its constituent particles and the distribution of particle sizes, contribute to variability. The required properties of the powder particles are :

Less cohesive and adhesive particles through corrugated surfaces,

low bulk density,

reduced surface energy and particle interaction to facilitate deaggregation

reducing aerodynamic diameters through particle engineering

To achieve these, incorporation into carriers

Unlike liquid solutions or gas mixtures, powders are never completely homogeneous (at primary particulate scale) and segregation by size, which is a function of external forces, is always a potential problem. The aerodynamic behavior, which has a profound effect on the disposition of drug from a DPI, is particularly sensitive to powder properties.

The different factors important in formulation of dry powders for inhalation include :

Crystallinity and Polymorphism

Moisture Content and Hygroscopicity

Particle Size

Aerodynamic Diameter and Dynamic Shape Factor

Fine-Particle Fraction


Surface Area and Morphology

Crystallinity and Polymorphism :

Nearly one third of all drugs are known to display polymorphism, 40 which is the ability of a solid to exist in more than one crystal from. A prominent example of a polymorphic pharmaceutical is carbamazepine, which has 4 known polymorphs. Different polymorphs are at different energy states and thus have different properties, including stability, solubility, and even bioavailability.

It is also possible to generate a noncrystalline solid. In most cases this involves cooling a fluid so rapidly that its

molecules lose mobility before assuming their lattice positions. A noncrystalline material is considered amorphous because it lacks long-range order. Amorphous materials have higher Gibbs free energies than crystals; thermodynamic laws predict that, in the long-term, materials seek to minimize their free energies by transitioning to lower energy states (eg, crystallization). Whether this will occur at a timescale that need be of concern to the pharmaceutical scientist is governed by the chemical kinetics of the system. Polymorphs usually differ in density, melting point, solubility, and hygroscopicity. The most stable polymorph frequently has the highest density, highest melting point, and lowest solubility. Discriminating analytical methods to characterize polymorphs include x-ray diffraction and thermal analysis, such as differential scanning calorimetry.

Current commercial Salbutamol formulations

Salbutamol 100mcg + Beclomethasone 50mcg


Aerocort Hfa

Salbutamol 100mcg + Beclomethasone 50mcg

Ecopack Inhaler


Salbutamol 100mcg + Beclomethasone 50mcg



Salbutamol 100mcg + Ipratropium 20mcg



Salbutamol 100mcg + Sodium Cromoglycate 1mg



Salbutamol 2.5mg + Ipratropium 500mcg Per 2.5ml



Salbutamol 2.5mg + Ipratropium 500mcg Per Ml

Respirator Soln


Salbutamol 200mcg + Beclomethasone 100mcg



Salbutamol 200mcg + Ipratropium 40mcg



Salbutamol 400mcg + Beclomethasone 200mcg


Aerocort Forte

Salbutamol 100mcg

Ecopack Inhaler

Asthalin Hfa

Salbutamol 100mcg

Ecopack Inhaler


Salbutamol 100mcg

Ecopack Inhaler


Salbutamol + Ambroxol Hcl


Axalin - Ax

Salbutamol 100mcg



Salbutamol 2.5mg Per 2.5ml



Salbutamol 200mcg



Salbutamol 2mg



Salbutamol 2mg Per 5ml



Salbutamol 4mg



Salbutamol 4mg Sa


Asthalin Sa-4

Salbutamol 5mg Per Ml

Resp Solution


Salbutamol 8mg Sa


Asthalin Sa-8

Principles of Techniques used for Preparation and characterization of the formulations


The microfluidizer model used for the study was M-110S. It has an air driven pump that supplies air at the desired pressure to the product stream. As the pump strokes to and fro and completes 1 cycle, the product gets forced through the precisely defined fixed geometry microchannels within the interaction chamber. The product passes through the chamber with high velocity and creates very high shear rates. Owing to the geometry of the microchannels in the interaction chamber, the force exerted on the product is uniform throughout. This produces unique results such as uniform particles with size reduction (often submicron). For these studies, there was no use of cooling coil and bath to keep the sample in chamber at low temperature. This caused heating and subsequent agglomeration, that needed post-micronized cooling and sonication.

The specifications of the instrument are as follows :

Particle Size Distribution

Laser diffraction particle size analysis is based on the principle that all particles scatter light at a range of angles which are characteristic of their size. Larger particles scatter light at a low angle of diffraction and vice versa for small particles. The Mastersizer Microplus uses a He-Ne laser as a light source, which illuminates the particle in the measuring zone. This is then focussed by a Fourier lens to a detector which consists of a large number of photosensitive elements radiating outward from the centre. This collects the scattered light from an ensemble of particles and overlays the common angles of scattering on the detector array. The intensity of the scattered light is measured and using an optical model (Mie theory) to calculate the scattering pattern and a mathematical deconvolution procedure, a volumetric particle size distribution is calculated that best matches the measured pattern.

In order to convert the scattering pattern obtained from these particles to an actual particle size distribution, the Malvern software makes use of a "Presentation", which is a predicted scattering pattern from theoretical particles. The Presentation takes into account specific information about the particles and the material that they are suspended in, such as the relative refractive index of the particles, the absorption properties of the particles (known as the imaginary refractive index) and the refractive index of the dispersant, so that it can calculate exactly how light passes through them. Use of correct Presentation is importantfor smaller particles (below 10 microns), and also when the refractive indices of particles and dispersant are close. The refractive indices of Salbutamol sulphate and Isooctane are 1.553 and 1.3915 respectively.

Spray Dryer

The spray drying process consists of 5 stages : (1) Atomisation of feed into spray of droplets, (2) spray-air contact and droplet/particle flow, (3) evaporation of solvent, (4) separation of particles from drying air, and (5) dried product handling for further use.

Atomisation transforms the liquid feed entering the spray-drying nozzle into a droplet cloud that once contacted with hot drying air provides optimum conditions for solvent evaporation. Liquid feed and atomising gas (typically compressed air or inert gas like nitrogen) are passed through the nozzle simultaneously. The high air velocity generated in the nozzle then breaks up the liquid into a spray of fine droplets, which can produce fine powders of <10 microns in size. Spray-air contact results in rapid evaporation with short drying times. Heat transfer to the particle is by convection from air to the drying droplets and a saturated vapour film rapidly develops at the droplet surface where evaporation of volatile solvent takes place. Solvent diffusion to the surface maintains saturated conditions at the surface, and evaporation takes place at a constant rate - primary drying. When the volatile content becomes too low to maintain surface saturation, the critical point is reached and a dried layer of material forms at the surface. Further evaporation of solvent is now dependent upon diffusion through this surface layer - secondary drying, and the thickness of the layer increases with time until a solid particle is formed. During evaporation, thebspray distribution undergoes a variety of size and shape changes, and the resultant particle distribution shows a degree of polydispersity. Particles are separated from the drying air by means of cyclones. These separations are critical for maximizing the product yield and previous studies have shown upto 90% yield for inhalation powders. The circulation of air within cyclone produces a centrifugal force on entrained spray dried particles. The consequence is radially outwards and downward movement of particles before impacting on the walls of the cyclone or collection bottle. The powder is physically removed by scraping the vessel walls.


X-Ray Diffraction

XRPD was used to determine the crystallinity of the spray dried powder sample, i.e. amorphous, partially amorphous or crystalline. In XRPD, the generated X-rays are collimated and directed onto the sample, where part of the beam is absorbed, refracted, scattered, and most importantly, diffracted. The diffraction distance between the d-spacings (planes of atoms) is measured using Bragg's law :

nλ = 2d.sinθ

where, n=order of diffracted beam, d=distance between adjacent planes of atoms, λ=wavelength of incident X-ray beam, θ= angle of incidence of X-ray beam.

The characteristic set of d-spacings generated in an X-ray scan gives a unique fingerprint of the material. The crystalline form is characterized by number of sharp and narrow peaks within the XRPD pattern. The amorphous materials, owing to their lack of long-range order of packaging of molecules, do not give peaks. Amorphous material is generated in spray drying, as rapid evaporation of solvent inhibits the molecules to align in crystal form.

Raman Spectroscopy

Scanning Electron Microscopy

Next Generation Impactor

Inverse Gas Chromatography

Differential Scanning Calorimetry

Hypothesis for the project